Rest–activity rhythm as a clinical biomarker in cancer
Authors: Pasquale F Innominato, Nicholas I Wreglesworth, Abdoulaye Karaboué, David Spiegel, Francis A Lévi
Journal: The Lancet Healthy Longevity (2023)

In their Article, Hongliang Feng and colleagues1Feng H Yang L Ai S et al.Association between accelerometer-measured amplitude of rest–activity rhythm and future health risk: a prospective cohort study of the UK Biobank.Lancet Healthy Longev. 2023; 4: e200-e210Summary Full Text Full Text PDF Google Scholar analysed accelerometer time series data and showed a strong association between a low amplitude of rest–activity rhythm and increased disease incidence and mortality. The authors’ findings support the previously acknowledged link between circadian disruption and cancer risk.2Ward EM Germolec D Kogevinas M et al.Carcinogenicity of night shift work.Lancet Oncol. 2019; 20: 1058-1059Summary Full Text Full Text PDF PubMed Scopus (0) Google Scholar We commend their thorough analytical approach in such a large dataset. However, we would encourage the authors to further substantiate their analysis by including the actigraphic dichotomy index (I<O) in their list of parameters. I<O is a metric that integrates the circadian regulation of sleep and activity by considering physical activity and rest over 24 h differently from relative amplitude. I<O represents the percentage of minutes during an individual's rest span in which their activity level is lower than their median activity during the bout of wakefulness.3Lévi F Dugué PA Innominato P et al.Wrist actimetry circadian rhythm as a robust predictor of colorectal cancer patients survival.Chronobiol Int. 2014; 31: 891-900Crossref PubMed Google Scholar Of 30 wrist actigraphy parameters tested for clinical relevance, I<O ranked as the best predictor of clinical outcomes, consistently outperforming other parameters in nine prospective cancer studies from our group. I<O independently predicted overall survival in an individual patient-level meta-analysis involving 436 patients with metastatic colorectal cancer,3Lévi F Dugué PA Innominato P et al.Wrist actimetry circadian rhythm as a robust predictor of colorectal cancer patients survival.Chronobiol Int. 2014; 31: 891-900Crossref PubMed Google Scholar with confirmation of success reported in an independent meta-analysis of six studies involving 659 patients with cancer.4Kos M Brouwer CG van Laarhoven HWM Hopman MTE van Oijen MGH Buffart LM The association between wearable device metrics and clinical outcomes in oncology: a systematic review with evidence synthesis and meta-analysis.Crit Rev Oncol Hematol. 2023; 185103979 Crossref Scopus (0) Google Scholar I<O was also the most discriminatory behavioural marker between 226 patients with cancer and 182 healthy control individuals, outperforming both physical activity and sleep parameters.5Natale V Innominato PF Boreggiani M et al.The difference between in bed and out of bed activity as a behavioral marker of cancer patients: a comparative actigraphic study.Chronobiol Int. 2015; 32: 925-933Crossref PubMed Scopus (20) Google Scholar The significant association of I<O with health-related quality of life and the successful prediction of emergency hospitalisation further highlights the clinical relevance of this metric for patients with cancer. The UK Biobank dataset provides a unique opportunity to investigate whether I<O can also help to predict the incidence of (and mortality from) the main causes of morbidity and mortality, including cancer. Including I<O in the list of accelerometer-derived parameters used in Feng and colleagues’ analysis of the UK Biobank dataset could enhance the predictive value of circadian rhythm alterations for disease incidence and mortality, complementing the important results already shown in the Article. The authors provide compelling evidence that circadian dysregulation has a pervasive effect on human health, particularly by increasing cancer mortality. These practice-changing results call for the design of optimal diagnostic methods to assess rest–activity rhythm, and of dedicated interventions that target the actionable circadian determinants of clinical outcomes for patients with cancer and other major diseases. We declare no competing interests. Association between accelerometer-measured amplitude of rest–activity rhythm and future health risk: a prospective cohort study of the UK BiobankOur results suggest that low rest–activity rhythm amplitude might contribute to major health outcomes and provide further evidence to promote risk-modifying strategies associated with rest–activity rhythm to improve health and longevity. Full-Text PDF Open AccessRest–activity rhythm as a clinical biomarker in cancer – Authors' replyWe thank Pasquale F Innominato and colleagues for their important comments on our Article.1 We agree that our study could be improved by including the actigraphic dichotomy index (I<O), an index of rest–activity rhythm.2 A low I<O indicates weak rest–activity rhythmicity. Similarly to relative amplitude, I<O is insensitive to the absolute value and outliers of activity and does not rely on the shape of rest–activity rhythm. This index has been shown to be an excellent predictor of clinical outcomes such as survival, particularly among patients with cancer. Full-Text PDF Open Access